Adrenergic receptors (ARs) are the primary targets of catecholamines released from the sympathetic nerve endings during their activation. ARs play a central role in autonomic nervous system and serve as important targets of widely used drugs. Several ARs gene polymorphisms were found to be associated with cardiovascular disease in previous clinical studies. Although more precise mechanism of the polymorphisms influence on autonomic control of cardiovascular system was studied in many previous physiological studies, their results are not unequivocal. This paper reviews the results of clinical and physiological studies focused on the impact of selected common single nucleotide polymorphisms of ARs genes involved in sympathetic control on cardiovascular system and its control. In summary, many studies assessed only a very limited range of cardiovascular control related parameters providing only very limited view on the complex cardiovascular control. The overview of partially contradicting results underlines a need to examine wider range of cardiovascular measures including their reactivity under various stress conditions requiring further study. It is expected that an effect of one given polymorphism is not very prominent, but it is suggested that even subtle differences in cardiovascular control could - on a longer time scale - lead to the development of severe pathological consequences.

Department of Physiology Comenius University in Bratislava Jessenius Faculty of Medicine in Martin Martin Slovakia

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ADEFURIN A, GHIMIRE LV, KOHLI U, MUSZKAT M, SOFOWORA GG, LI C, PARANJAPE SY, STEIN CM, KURNIK D. Genetic variation in the α 1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J. 2015;15:310–315. doi: 10.1038/tpj.2014.69. PubMed DOI PMC

AHLES A, ENGELHARDT S. Polymorphic variants of adrenoceptors: pharmacology, physiology, and role in disease. Pharmacol Rev. 2014;66:598–637. doi: 10.1124/pr.113.008219. PubMed DOI

ARADILLAS-GARCÍA C, CRUZ M, PÉREZ-LUQUE E, GARAY-SEVILLA ME, MALACARA JM, ADUNA R, PERALTA J, BURGUETE-GARCÍA A, ALEGRÍA-TORRES JA. Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis Potosí and León, México. J Biomed Res. 2017;31:40–46. doi: 10.7555/JBR.30.20150169. PubMed DOI PMC

ATALA MM, GOULART A, GUERRA GM, MOSTARDA C, RODRIGUES B, MELLO PR, CASARINE DE, IRIGOYEN M-C, PEREIRA AC, CONSOLIM-COLOMBO FM. Arg16Gly and Gln27Glu β2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians. Am J Transl Res. 2015;7:153–161. PubMed PMC

BAKER JG, PROUDMAN RGW, HILL SJ. Impact of polymorphic variants on the molecular pharmacology of the two-agonist conformations of the human β1-adrenoceptor. LoS One. 2013;8:32–36. doi: 10.1371/journal.pone.0077582. PubMed DOI PMC

BRUCK H, LEINEWEBER K, TEMME T, WEBER M, HEUSCH G, PHILIPP T, BRODDE OE. The Arg389Gly Beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity. J Am Coll Cardiol. 2005;46:2111–2115. doi: 10.1016/j.jacc.2005.08.041. PubMed DOI

BRUNTON L, PARKER K, BLUMENTHAL D, BUXTON I. Goodman & Gilman’s: Manual of Pharmacology and Therapeutics. Pharmacol Ther. 2008

BÜSCHER R, BELGER H, EILMES KJ, TELLKAMP R, RADKE J, DHEIN S, HOYER PF, MICHEL MC, INSEL PA, BRODDE OE. In-vivo studies do not support a major functional role for the Gly389Arg β1-adrenoceptor polymorphism in humans. harmacogenetics. 2001;11:199–205. doi: 10.1097/00008571-200104000-00003. PubMed DOI

CAPOTE LA, MENDEZ PEREZ R, LYMPEROPOULOS A. GPCR signaling and cardiac function. Eur J Pharmacol. 2015;763:143–148. doi: 10.1016/j.ejphar.2015.05.019. PubMed DOI

CHEN Liping, XIAO T, CHEN Liling, XIE S, DENG M, WU D. The Association of ADRB1 and CYP2D6 polymorphisms with antihypertensive effects and analysis of their contribution to hypertension risk. Am J Med Sci. 2018;355:235–239. doi: 10.1016/j.amjms.2017.11.002. PubMed DOI

CICCARELLI M, SORRIENTO D, COSCIONI E, IACCARINO G, SANTULLI G. Endocrinology of the Heart in Health and Disease. Academic Press; 2017. Chapter 11 - Adrenergic Receptors; pp. 285–315. DOI

CRAWFORD DC, NICKERSON DA. Definition and clinical importance of haplotypes. Annu Rev Med. 2005;56:303–320. doi: 10.1146/annurev.med.56.082103.104540. PubMed DOI

DAGHESTANI MHMH, WARSY A, DAGHESTANI MHMH, AL-ODAIB AN, ELDALI A, AL-EISA NA, OMER SA, HASSAN ZK. Arginine 16 glycine polymorphism in β2-adrenergic receptor gene is associated with obesity, hyperlipidemia, hyperleptinemia, and insulin resistance in saudis. Int J Endocrinol. 2012;2012:945608. doi: 10.1155/2012/945608. PubMed DOI PMC

DAGHESTANI MM, DAGHESTANI MM, DAGHISTANI M, ELDALI A, HASSAN ZK, ELAMIN MH, WARSY A. ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1. Lipids Health Dis. 2018;17:58. doi: 10.1186/s12944-018-0679-7. PubMed DOI PMC

DOCHERTY JR. The pharmacology of α1-adrenoceptor subtypes. Eur J Pharmacol. 2019;855:305–320. doi: 10.1016/j.ejphar.2019.04.047. PubMed DOI

EISENACH JH, MCGUIRE AM, SCHWINGLER RM, TURNER ST, JOYNER MJ, EISENACH JH, MCGUIRE AM, SCHWINGLER RM, TURNER ST, JOYNER MJ, TURNER ST, JOYNER MJ, ARG T. The Arg16 / Gly β 2 -adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise The Arg16 / Gly β 2 -adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise. Physiol Genomics. 2012;16:323–328. doi: 10.1152/physiolgenomics.00152.2003. PubMed DOI

EISENACH JH, SCHROEDER DR, PAVEY ES, PENHEITER AR, KNUTSON JN, TURNER ST, JOYNER MJ. Interactions between beta-2 adrenoceptor gene variation, cardiovascular control and dietary sodium in healthy young adults. J Physiol. 2014;592:5221–5233. doi: 10.1113/jphysiol.2014.276469. PubMed DOI PMC

FLORDELLIS C, PARIS H, KARABINIS A, LYMPEROPOULOS A. Pharmacogenomics of adrenoceptors. Pharmacogenomics. 2004;5:803–817. doi: 10.1517/14622416.5.7.803. PubMed DOI

FREITAS SR, PEREIRA AC, FLORIANO MS, MILL JG, KRIEGER JE. Association of alpha1a-adrenergic receptor polymorphism and blood pressure phenotypes in the Brazilian population. BMC Cardiovasc Disord. 2008;8:1–7. doi: 10.1186/1471-2261-8-40. PubMed DOI PMC

GJESING AP, ANDERSEN G, ALBRECHTSEN A, GLÜMER C, BORCH-JOHNSEN K, JØRGENSEN T, HANSEN T, PEDERSEN O. Studies of associations between the Arg389Gly polymorphism of the β1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects. Diabet Med. 2007;24:392–397. doi: 10.1111/j.1464-5491.2006.02031.x. PubMed DOI

GREEN SA, TURKI J, BEJARANO P, HALL IP, LIGGETT SB. Influence of beta 2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells. Am J Respir Cell Mol Biol. 1995;13:25–33. doi: 10.1165/ajrcmb.13.1.7598936. PubMed DOI

GREEN SA, TURKI J, INNIS M, LIGGETT SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. iochemistry. 1994;33:9414–9419. doi: 10.1021/bi00198a006. PubMed DOI

GRUDELL ABM, SWEETSER S, CAMILLERI M, ECKERT DJ, VAZQUEZ-ROQUE MI, CARLSON PJ, BURTON DD, BRADDOCK AE, CLARK MM, GRASZER KM, KALSY SA, ZINSMEISTER AR. A Controlled pharmacogenetic trial of sibutramine on weight loss and body composition in obese or overweight adults. Gastroenterology. 2008;135:1142–1154. doi: 10.1053/j.gastro.2008.07.009. PubMed DOI PMC

GU D, GE D, SNIEDER H, HE J, CHEN S, HUANG J, LI B, CHEN R, QIANG B. Association of α1A adrenergic receptor gene variants on chromosome 8p21 with human stage 2 hypertension. J Hypertens. 2006;24:1049–1056. doi: 10.1097/01.hjh.0000226194.21311.2f. PubMed DOI

HANCHARD NA. Genetic susceptibility and single-nucleotide polymorphisms. Semin Fetal Neonatal Med. 2005;10:283–289. doi: 10.1016/j.siny.2005.01.001. PubMed DOI

HERNÁNDEZ-PACHECO G, GONZÁLEZ-HERMOSILLO A, MURATA C, YESCAS P, ESPÍNOLA-ZAVALETA N, MARTÍNEZ M, SERRANO H. Arg347Cys polymorphism of α1a-adrenergic receptor in vasovagal syncope. Case-control study in a Mexican population. Auton Neurosci Basic Clin. 2014;183:66–71. doi: 10.1016/j.autneu.2014.01.005. PubMed DOI

HUNTGEBURTH M, LA ROSÉE K, TEN FREYHAUS H, BÖHM M, SCHNABEL P, HELLMICH M, ROSENKRANZ S. The Arg389Gly β 1-adrenoceptor gene polymorphism influences the acute effects of β-adrenoceptor blockade on contractility in the human heart. Clin Res Cardiol. 2011;100:641–647. doi: 10.1007/s00392-011-0288-1. PubMed DOI

IACOVIELLO M, FORLEO C, SORRENTINO S, ROMITO R, DE TOMMASI E, LUCARELLI K, GUIDA P, PITZALIS MV. Alpha- and beta-adrenergic receptor polymorphisms in hypertensive and normotensive offspring. J Cardiovasc Med. 2006;7:316–321. doi: 10.2459/01.JCM.0000223252.34611.87. PubMed DOI

de JESUS ÍC, ALLE LF, MUNHOZ EC, da SILVA LR, LOPES WA, TURECK LV, PURIM KSM, TITSKI ACK, LEITE N. Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents. J Pediatr. 2018;94:425–431. doi: 10.1016/j.jped.2017.07.010. PubMed DOI

JIANG S, MAO G, ZHANG S, HONG X, TANG G, LI Z, LIU X, ZHANG Y, WANG B, XU X, WANG X. Individual and joint association of α1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects. Clin Pharmacol Ther. 2005;78:239–248. doi: 10.1016/j.clpt.2005.06.003. PubMed DOI

JOHNSON AD, NEWTON-CHEH C, CHASMAN DI, EHRET GB, JOHNSON T, ROSE L, RICE K, VERWOERT GC, LAUNER LJ, GUDNASON V, LARSON MG, CHAKRAVARTI A, PSATY BM, CAULFIELD M, VAN DUIJN CM, RIDKER PM, MUNROE PB, LEVY D. Association of hypertension drug target genes with blood pressure and hypertension in 86 588 individuals. Hypertension. 2011;57:903–910. doi: 10.1161/HYPERTENSIONAHA.110.158667. PubMed DOI PMC

JOHNSON JA, ZINEH I, PUCKETT BJ, MCGORRAY SP, YARANDI HN, PAULY DF. BETA;1-Adrenergic Receptor Polymorphisms and Antihypertensive Response To Metoprolol. Clin Pharmacol Ther. 2003;74:44–52. doi: 10.1016/S0009-9236(03)00068-7. PubMed DOI

JOSEPH SS, LYNHAM JA, GRACE AA, COLLEDGE WH, KAUMANN AJ. Markedly reduced effects of (−)-isoprenaline but not of (−)-CGP12177 and unchanged affinity of beta-blockers at Gly389-beta1-adrenoceptors compared to Arg389-beta1-adrenoceptors. Br J Pharmacol. 2004;142:51–56. doi: 10.1038/sj.bjp.0705753. PubMed DOI PMC

KATSAROU M-S, KARATHANASOPOULOU A, ANDRIANOPOULOU A, DESINIOTIS V, TZINIS E, DIMITRAKIS E, LAGIOU M, CHARMANDARI E, ASCHNER M, TSATSAKIS AM, CHROUSOS GP, DRAKOULIS N. Beta 1, Beta 2 and Beta 3 adrenergic receptor gene polymorphisms in a Southeastern European population. Front Genet. 2018;9 doi: 10.3389/fgene.2018.00560. PubMed DOI PMC

KELLEY EF, SNYDER EM, JOHNSON BD. Influence of Beta-1 adrenergic receptor genotype on cardiovascular response to exercise in healthy subjects. Cardiol Res. 2018;9:343–349. doi: 10.14740/cr785. PubMed DOI PMC

KELSEY RM, ALPERT BS, DAHMER MK, KRUSHKAL J, QUASNEY MW. Alpha-adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults. sychophysiology. 2012;49:401–412. doi: 10.1111/j.1469-8986.2011.01319.x. PubMed DOI PMC

KENAKIN T. New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2. Br J Pharmacol. 2013;168:554–575. doi: 10.1111/j.1476-5381.2012.02223.x. PubMed DOI PMC

KIM S, MISRA A. SNP genotyping: technologies and biomedical applications. Annu Rev Biomed Eng. 2007;9:289–320. doi: 10.1146/annurev.bioeng.9.060906.152037. PubMed DOI

KINDERMANN M, SEELAND U, RUHNKE P, BÖHM M, MAACK C. Functional effects of β1-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without b-blocker administration. Clin Res Cardiol. 2011;100:129–137. doi: 10.1007/s00392-010-0221-z. PubMed DOI

KOMARA M, VASUDEVAN R, ISMAIL P, BAKAR SA, PISHVA SR, HEIDARI F. Association of beta 2 adrenoceptor gene polymorphisms in Malaysian hypertensive subjects. Genet Mol Res. 2014;13:2939–2948. doi: 10.4238/2014.April.16.2. PubMed DOI

KUMAR S, MISHRA A, SRIVASTAVA A, MITTAL T, GARG N, MITTAL B. Significant role of ADRB3 rs4994 towards the development of coronary artery disease. Coron Artery Dis. 2014;25:29–34. doi: 10.1097/MCA.0000000000000056. PubMed DOI

KUNEŠ J, ZICHA J. The interaction of genetic and environmental factors in the etiology of hypertension. Physiol Res. 2009;58:33–42. doi: 10.33549/physiolres.931913. PubMed DOI

KURNIK D, MUSZKAT M, LI C, SOFOWORA GG, FRIEDMAN EA, SCHEININ M, WOOD AJJ, STEIN CM. Genetic variations in the α(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine. irc Cardiovasc Genet. 2011;4:179–187. doi: 10.1161/CIRCGENETICS.110.957662. PubMed DOI PMC

LA ROSÉE K, HUNTGEBURTH M, ROSENKRANZ S, BÖHM M, SCHNABEL P. The Arg389Gly beta1-adrenoceptor gene polymorphism determines contractile response to catecholamines. Pharmacogenetics. 2004;14:711–716. doi: 10.1097/00008571-200411000-00001. PubMed DOI

LEE HY, CHUNG WJ, JEON HK, SEO HS, CHOI DJ, JEON ES, KIM JJ, SHIN JH, KANG SM, LIM SC, BAEK SH. Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in korean heart failure patients: Association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study. Korean J Intern Med. 2016;31:277–287. doi: 10.3904/kjim.2015.043. PubMed DOI PMC

LEI B, MORRIS DP, SMITH MP, SVETKEY LP, NEWMAN MF, ROTTER JI, BUCHANAN TA, BECKSTROM-STERNBERG SM, GREEN ED, SCHWINN DA. Novel human α1a-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function. Naunyn Schmiedebergs Arch Pharmacol. 2005;371:229–239. doi: 10.1007/s00210-005-1019-9. PubMed DOI PMC

LEINEWEBER K, BRODDE OE. β2-adrenoceptor polymorphisms: Relation between in vitro and in vivo phenotypes. Life Sci. 2004;74:2803–2814. doi: 10.1016/j.lfs.2003.10.025. PubMed DOI

LEINEWEBER K, BRUCK H, TEMME T, HEUSCH G, PHILIPP T, BRODDE O. The Arg389Gly beta1-adrenoceptor polymorphism does not affect cardiac effects of exercise after parasympathetic inhibition by atropine. harmacogenet Genomics. 2006;16:9–13. doi: 10.1097/01.fpc.0000184956.16077.93. PubMed DOI

LEINEWEBER K, BÜSCHER R, BRUCK H, BRODDE O-E. Beta-adrenoceptor polymorphisms. Naunyn Schmiedebergs Arch Pharmacol. 2004;369:1–22. doi: 10.1007/s00210-003-0824-2. PubMed DOI

LEVIN MC, MARULLO S, MUNTANER O, ANDERSSON B, MAGNUSSON Y. The myocardium-protective Gly-49 variant of the β1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem. 2002;277:30429–30435. doi: 10.1074/jbc.M200681200. PubMed DOI

LI Y, YUAN H, SUN L, ZHOU Q, YANG F, YANG Z, LIU D. β 2 -Adrenergic Receptor Gene Polymorphisms Are Associated with Cardiovascular Events but not All-Cause Mortality in Coronary Artery Disease Patients: A Meta-Analysis of Prospective Studies. Genet Test Mol Biomarkers. 2019;23:124–137. doi: 10.1089/gtmb.2018.0153. PubMed DOI PMC

LI YY, LU XZ, WANG H, ZHOU YH, YANG XX, GENG HY, GONG G, KIM HJ. ADRB3 gene Trp64Arg polymorphism and essential hypertension: A meta-analysis including 9,555 subjects. Front Genet. 2018;9:1–10. doi: 10.3389/fgene.2018.00106. PubMed DOI PMC

LIMA JJ, FENG H, DUCKWORTH L, WANG J, SYLVESTER JE, KISSOON N, GARG H. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism. 2007;56:757–765. doi: 10.1016/j.metabol.2007.01.007. PubMed DOI PMC

LYMPEROPOULOS A, CORA N, MANING J, BRILL AR, SIZOVA A. Signaling and function of cardiac autonomic nervous system receptors: Insights from the GPCR signalling universe. FEBS J. 2021;288:2645–2659. doi: 10.1111/febs.15771. PubMed DOI

MAHESH KUMAR KN, RAMU P, RAJAN S, SHEWADE DG, BALACHANDER J, ADITHAN C. Genetic polymorphisms of beta1 adrenergic receptor and their influence on the cardiovascular responses to metoprolol in a South Indian population. J Cardiovasc Pharmacol. 2008;52:459–466. doi: 10.1097/FJC.0b013e31818d3878. PubMed DOI

MASON DA, MOORE JD, GREEN SA, LIGGETT SB. A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999;274:12670–12674. doi: 10.1074/jbc.274.18.12670. PubMed DOI

MASUO K, KATSUYA T, FU Y, RAKUGI H, OGIHARA T, TUCK ML. BETA;2-Adrenoceptor Polymorphisms Relate To Insulin Resistance and Sympathetic Overactivity As Early Markers of Metabolic Disease in Nonobese, Normotensive Individuals. Am J Hypertens. 2005a;18:1009–1014. doi: 10.1016/j.amjhyper.2005.01.006. PubMed DOI

MASUO K, KATSUYA T, FU Y, RAKUGI H, OGIHARA T, TUCK ML. BETA;2- and BETA;3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years. Circulation. 2005b;111:3429–3434. doi: 10.1161/CIRCULATIONAHA.104.519652. PubMed DOI

MATSUNAGA T, YASUDA K, ADACHI T, GU N, YAMAMURA T, MORITANI T, TSUJIMOTO G, TSUDA K. Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population. J Hum Genet. 2007a;52:28–37. doi: 10.1007/s10038-006-0076-3. PubMed DOI

MATSUNAGA T, YASUDA K, ADACHI T, GU N, YAMAMURA T, MORITANI T, TSUJIMOTO G, TSUDA K. Association of β-adrenoceptor polymorphisms with cardiac autonomic modulation in Japanese males. Am Heart J. 2007b;154:759–766. doi: 10.1016/j.ahj.2007.03.053. PubMed DOI

McCAFFERY JM, POGUE-GEILE MF, FERRELL RE, PETRO N, MANUCK SB. Variability within α- and β-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge. J Hypertens. 2002;20:1105–1114. doi: 10.1097/00004872-200206000-00021. PubMed DOI

MICHEL LYM, FARAH C, BALLIGAND JL. The Beta3 Adrenergic Receptor in Healthy and Pathological Cardiovascular Tissues. 2020;9:1–22. doi: 10.3390/cells9122584. PubMed DOI PMC

MIRRAKHIMOV AE, KERIMKULOVA AS, LUNEGOVA OS, MOLDOKEEVA CB, ZALESSKAYA YV, ABILOVA SS, SOVHOZOVA NA, ALDASHEV AA, MIRRAKHIMOV EM. An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances. Cardiovasc Diabetol. 2011;10:1–7. doi: 10.1186/1475-2840-10-89. PubMed DOI PMC

MITRA SR, TAN PY, AMINI F. Association of ADRB2 rs1042713 with obesity and obesity-related phenotypes and its interaction with dietary fat in modulating glycaemic indices in malaysian adults. J Nutr Metab. 2019;2019:8718795. doi: 10.1155/2019/8718795. PubMed DOI PMC

NEWTON-CHEH C, GUO CY, WANG TJ, O’DONNELL CJ, LEVY D, LARSON MG. Genome-wide association study of electrocardiographic and heart rate variability traits: The Framingham Heart Study. BMC Med Genet. 2007;8:1–8. doi: 10.1186/1471-2350-8-S1-S7. PubMed DOI PMC

NUNES RAB, BARROSO LP, DA COSTA PEREIRA A, KRIEGER JE, MANSUR AJ. Gender-related associations of genetic polymorphisms of α-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B2 receptor with treadmill exercise test responses. Open Hear. 2014;1 doi: 10.1136/openhrt-2014-000132. PubMed DOI PMC

Encyclopedia of Genetics. Academic Press; New York: 2001. OHTA T: Selective Neutrality; pp. 1800–1803. DOI

PIÉTRI-ROUXEL F, ST JOHN MANNING B, GROS J, STROSBERG AD. The biochemical effect of the naturally occurring Trp64→Arg mutation on human β3-adrenoceptor activity. Eur J Biochem. 1997;247:1174–1179. doi: 10.1111/j.1432-1033.1997.01174.x. PubMed DOI

POLANCZYK G, ZENI C, GENRO JP, GUIMARÃES AP, ROMAN T, HUTZ MH, ROHDE LA. Association of the adrenergic α2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2007;64:218–224. doi: 10.1001/archpsyc.64.2.218. PubMed DOI

RANA BK, INSEL PA, PAYNE SH, ABEL K, BEUTLER E, ZIEGLER MG, SCHORK NJ, O’CONNOR DT. Population-based sample reveals gene-gender interactions in blood pressure in white Americans. Hypertension. 2007;49:96–106. doi: 10.1161/01.HYP.0000252029.35106.67. PubMed DOI

RANADE K, JORGENSON E, SHEU WH-H, PEI D, HSIUNG CA, CHIANG F, CHEN YI, PRATT R, OLSHEN RA, CURB D, COX DR, BOTSTEIN D, RISCH N. A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002;70:935–942. doi: 10.1086/339621. PubMed DOI PMC

RATHZ DA, BROWN KM, KRAMER LA, LIGGETT SB. Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking. J Cardiovasc Pharmacol. 2002;39:155–160. doi: 10.1097/00005344-200202000-00001. PubMed DOI

ROCHAIS F, VILARDAGA J-P, NIKOLAEV VO, BÜNEMANN M, LOHSE MJ, ENGELHARDT S. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J Clin Invest. 2007;117:229–235. doi: 10.1172/JCI30012. PubMed DOI PMC

ROKAMP KZ, STAALSOE JM, GARTMANN M, SLETGAARD A, NORDSBORG NB, SECHER NH, NIELSEN HB, OLSEN NV. G16R single nucleotide polymorphism but not haplotypes of the β2-adrenergic receptor gene alters cardiac output in humans. lin Sci. 2013;125:191–198. doi: 10.1042/CS20120555. PubMed DOI

ROSMOND R, BOUCHARD C, BJÖRNTORP P. A C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels. J Intern Med. 2002;251:252–257. doi: 10.1046/j.1365-2796.2002.00961.x. PubMed DOI

RYUK JA, ZHANG X, KO BS, DAILY JW, PARK S. Association of β3-adrenergic receptor rs4994 polymorphisms with the risk of type 2 diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2017;129:86–96. doi: 10.1016/j.diabres.2017.03.034. PubMed DOI

SANDILANDS AJ, O’SHAUGHNESSY KM, YASMIN BETA;1-adrenoreceptor polymorphisms and blood pressure: 49S variant increases plasma renin but not blood pressure in hypertensive patients. Am J Hypertens. 2019;32:447–451. doi: 10.1093/ajh/hpz019. PubMed DOI PMC

SCHMITZ M, DENARDIN D, SILVA TL, PIANCA T, ROMAN T, HUTZ MH, FARAONE SV, ROHDE LA. Association Between Alpha-2a-adrenergic Receptor Gene and ADHD Inattentive Type. Biol Psychiatry. 2006;60:1028–1033. doi: 10.1016/j.biopsych.2006.02.035. PubMed DOI

SHAHIN MH, El ROUBY N, CONRADO DJ, GONZALEZ D, GONG Y, LOBMEYER MT, BEITELSHEES AL, BOERWINKLE E, GUMS JG, CHAPMAN A, TURNER ST, PEPINE CJ, COOPER-DEHOFF RM, JOHNSON JA. β2-Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies. J Clin Pharmacol. 2019;59:1462–1470. doi: 10.1002/jcph.1443. PubMed DOI PMC

SHIBATA K, HIRASAWA A, MORIYAMA N, KAWABE K, OGAWA S, TSUJIMOTO G. α(1a)-adrenoceptor polymorphism: Pharmacological characterization and association with benign prostatic hypertrophy. Br J Pharmacol. 1996;118:1403–1408. doi: 10.1111/j.1476-5381.1996.tb15552.x. PubMed DOI PMC

SI D, WANG J, XU Y, CHEN X, ZHANG M, ZHOU H. Association of common polymorphisms in b1-adrenergic receptor with antihypertensive response to carvedilol. J Cardiovasc Pharmacol. 2014;64:306–309. doi: 10.1097/FJC.0000000000000119. PubMed DOI

SKINNER BW, CURTIS KA, GOODHART AL. Hypnotics and Sedatives. Side Eff Drugs Annu. 2018 doi: 10.1016/bs.seda.2018.06.002. DOI

SNAPIR A, KOSKENVUO J, TOIKKA J, ORHO-MELANDER M, HINKKA S, SARASTE M, HARTIALA J, SCHEININ M. Effects of common polymorphisms in the α1A-, α2B-, β1- and β2-adrenoreceptors on haemodynamic responses to adrenaline. Clin Sci. 2003;104:509–520. doi: 10.1042/CS20020299. PubMed DOI

SNIEDER H, DONG Y, BARBEAU P, HARSHFIELD GA, DALAGEOGOU C, ZHU H, CARTER ND, TREIBER FA. β2-adrenergic receptor gene and resting hemodynamics in European and African American youth. Am J Hypertens. 2002;15:973–979. doi: 10.1016/S0895-7061(02)02991-6. PubMed DOI

SNYDER EM, BECK KC, DIETZ NM, EISENACH JH, JOYNER MJ, TURNER ST, JOHNSON BD. Arg16Gly polymorphism of the β2-adrenergic receptor is associated with differences in cardiovascular function at rest and during exercise in humans. J Physiol. 2006;571:121–130. doi: 10.1113/jphysiol.2005.098558. PubMed DOI PMC

SOFOWORA GG, DISHY V, LANDAU R, XIE HG, PRASAD HC, BYRNE DW, SMILEY RM, KIM RB, WOOD AJJ, STEIN CM. α1A-Adrenergic receptor polymorphism and vascular response. Clin Pharmacol Ther. 2004;75:539–545. PubMed

SVOBODA P, TEISINGER J, NOVOTNÝ J, BOUŘOVÁ L, DRMOTA T, HEJNOVÁ L, MORAVCOVÁ Z, LISÝ V, RUDAJEV V, STÖHR J, VOKURKOVÁ A, ŠVANDOVÁ I, DURCHÁNKOVÁ D. Biochemistry of transmembrane signaling mediated by trimeric G proteins. Physiol Res. 2004;53(Suppl 1):S141–S152. PubMed

TAVERNIER G, TOUMANIANTZ G, ERFANIAN M, HEYMANN MF, LAURENT K, LANGIN D, GAUTHIER C. β3-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human β 3-adrenergic receptor. Cardiovasc Res. 2003;59:288–296. doi: 10.1016/S0008-6363(03)00359-6. PubMed DOI

TIKHONOFF V, HASENKAMP S, KUZNETSOVA T, THIJS L, JIN Y, RICHART T, ZHANG H, BRAND-HERRMANN SM, BRAND E, CASIGLIA E, STAESSEN JA. Blood pressure and metabolic phenotypes in relation to the ADRB1 Arg389Gly and ADRA2B I/D polymorphisms in a White population. J Hum Hypertens. 2008;22:864–867. doi: 10.1038/jhh.2008.73. PubMed DOI

WARNE T, EDWARDS PC, LESLIE AGW, TATE CG. Crystal structures of a stabilized β1-adrenoceptor bound to the biased agonists bucindolol and carvedilol. 2012;20:841–849. doi: 10.1016/j.str.2012.03.014. PubMed DOI PMC

WILK JB, MYERS RH, PANKOW JS, HUNT SC, LEPPERT MF, FREEDMAN BI, PROVINCE MA, ELLISON RC. Adrenergic receptor polymorphisms associated with resting heart rate: The HyperGEN study. Ann Hum Genet. 2006;70:566–573. doi: 10.1111/j.1469-1809.2005.00258.x. PubMed DOI

WITTWER ED, LIU Z, WARNER ND, SCHROEDER DR, NADEAU AM, ALLEN AR, MURILLO CJ, ELVEBAK RL, AAKRE BM, EISENACH JH. Beta-1 and beta-2 adrenergic receptor polymorphism and association with cardiovascular response to orthostatic screening. Auton Neurosci Basic Clin. 2011;164:89–95. doi: 10.1016/j.autneu.2011.07.004. PubMed DOI PMC

WU D, LI G, DENG M, SONG W, HUANG X, GUO X, WU Z, WU S, XU J. Associations between ADRB1 and CYP2D6 gene polymorphisms and the response to β-blocker therapy in hypertension. J Int Med Res. 2015;43:424–434. doi: 10.1177/0300060514563151. PubMed DOI

XIE C, HUA W, ZHAO Y, RUI J, FENG J, CHEN Y, LIU Y, LIU J, YANG X, XU X. The ADRB3 rs4994 polymorphism increases risk of childhood and adolescent overweight/obesity for East Asia’s population: an evidence-based meta-analysis. Adipocyte. 2020;9:77–86. doi: 10.1080/21623945.2020.1722549. PubMed DOI PMC

XIE HG, KIM RB, STEIN CM, GAINER JV, BROWN NJ, WOOD AJ. Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension. Pharmacogenetics. 1999;9:651–656. doi: 10.1097/00008571-199910000-00012. PubMed DOI

YAĞAR S, YAVAŞ S, KARAHALIL B. The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery. ol Biol Rep. 2011;38:3383–3389. doi: 10.1007/s11033-010-0446-y. PubMed DOI

YANG AC, TSAI S, HONG C, WANG C, CHEN T, LIOU Y, PENG C. Clustering Heart Rate Dynamics Is Associated with b - Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index. 2011;6 doi: 10.1371/journal.pone.0019232. PubMed DOI PMC

YANG H, CAI D, ZHU Q, WU D, WANG Q, WANG Z. The mutation of Trp64Arg in β3-adrenoreceptor-encoding gene is significantly associated with increased hypertension risk and elevated blood pressure: a meta-analysis. Oncotarget. 2017;8:46480–46490. doi: 10.18632/oncotarget.16666. PubMed DOI PMC

YANG L-KK, TAO Y-XX. Physiology and pathophysiology of the β 3 -adrenergic receptor. 1st ed. Prog. Mol. Biol. Transl. Sci. Elsevier Inc; Netherlands: 2019. PubMed DOI

ZHANG Y, HONG X, LIU H, HUO Y, XU X. Arg347Cys polymorphism of α1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients. J Hum Genet. 2009;54:360–364. doi: 10.1038/jhg.2009.42. PubMed DOI